Impairment of neutrophil functions and homeostasis in COVID-19 patients: association with disease severity DOI Creative Commons

Chloé Loyer,

Arnaud Lapostolle, Tomas Urbina

et al.

Critical Care, Journal Year: 2022, Volume and Issue: 26(1)

Published: May 30, 2022

Abstract Background A dysregulated immune response is emerging as a key feature of critical illness in COVID-19. Neutrophils are components early innate immunity that, if not tightly regulated, contribute to uncontrolled systemic inflammation. We sought decipher the role neutrophil phenotypes, functions, and homeostasis COVID-19 disease severity outcome. Methods By using flow cytometry, this longitudinal study compares peripheral whole-blood neutrophils from 90 ICU patients with those 22 SARS-CoV-2-negative hospitalized for severe community-acquired pneumonia (CAP) 38 healthy controls. also assessed correlations between these phenotypic functional indicators markers endothelial damage well severity. Results At admission, circulating showed continuous basal hyperactivation seen CAP patients, associated higher levels soluble E- P-selectin, which reflect platelet activation. Furthermore, had expanded aged-angiogenic reverse transmigrated subsets—both involved dysfunction vascular Simultaneously, significantly lower oxidative burst bacterial formyl peptide. Moreover dying expansion subset greater impairment than survivors. Conclusions These data suggest that exhaustion may be pathogenesis identify angiogenic potentially harmful fatal Graphic

Language: Английский

Next generation bioelectronic medicine: making the case for non-invasive closed-loop autonomic neuromodulation DOI Creative Commons
Imanuel Lerman,

Yifeng Bu,

Rahul Singh

et al.

Bioelectronic Medicine, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 20, 2025

Abstract The field of bioelectronic medicine has advanced rapidly from rudimentary electrical therapies to cutting-edge closed-loop systems that integrate real-time physiological monitoring with adaptive neuromodulation. Early innovations, such as cardiac pacemakers and deep brain stimulation, paved the way for these sophisticated technologies. This review traces historical technological progression medicine, culminating in emerging potential devices multiple disorders body. We emphasize both invasive techniques, implantable brain, spinal cord autonomic regulation, while we introduce new prospects non-invasive neuromodulation, including focused ultrasound newly developed neurography enabling precise detection titration inflammatory immune responses. case neuromodulation (incorporating splenic stimulation) is presented through its applications conditions sepsis chronic inflammation, illustrating capacity revolutionize personalized healthcare. Today, or have yet be dynamically modulate nervous system function by responding molecular signals; it represents a transformative approach therapeutic interventions major opportunity which may advance. Knowledge gaps remain likely contribute lack available closed loop systems, namely, (1) significant exogenous endogenous noise must filtered out, (2) drift signal due temporal change disease severity and/or therapy induced neuroplasticity, (3) confounding effects (e.g., concurrent medications dysregulate functions). Leveraging continuous feedback adjustments overcome many barriers, next generation stand at forefront precision offering avenues individualized treatment.

Language: Английский

Citations

2
Neutrophils and COVID-19: Active Participants and Rational Therapeutic Targets DOI Creative Commons
Jon Hazeldine, Janet M. Lord

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: June 2, 2021

Whilst the majority of individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative pathogen COVID-19, experience mild to moderate symptoms, approximately 20% develop complications that may progress distress syndrome, pulmonary failure and death. To date, single cell high-throughput systems based analyses peripheral immune responses SARS-CoV-2 suggest a hyperactive dysregulated response underpins development disease, prominent role assigned neutrophils. Characterised in part by robust generation neutrophil extracellular traps (NETs), presence immature, immunosuppressive activated subsets circulation, neutrophilic infiltrates lung, granulocytic signature is emerging as defining feature COVID-19. Furthermore, an assessment number, maturity status and/or function circulating neutrophils at time hospital admission has shown promise prognostic tool for early identification patients risk clinical deterioration. Here, summarising results studies have examined SARS-CoV-2, we provide comprehensive overview changes occur composition, phenotype pool COVID-19 differing disease severities discuss potential mediators SARS-CoV-2-induced dysfunction. With few specific treatments currently approved conclude review discussing whether represent therapeutic target treatment

Language: Английский

Citations

74
COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19 DOI Open Access
Michele Costanzo, Marianna Caterino, Roberta Fedele

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(5), P. 2414 - 2414

Published: Feb. 22, 2022

Omics-based technologies have been largely adopted during this unprecedented global COVID-19 pandemic, allowing the scientific community to perform research on a large scale understand pathobiology of SARS-CoV-2 infection and its replication into human cells. The application omics techniques has addressed every level application, from detection mutations, methods diagnosis or monitoring, drug target discovery, vaccine generation, basic definition pathophysiological processes biochemical mechanisms behind spread SARS-CoV-2. Thus, term COVIDomics wants include those efforts provided by omics-scale investigations with current research. This review summarizes diverse pieces knowledge acquired techniques, main focus proteomics metabolomics studies, in order capture common signature terms proteins, metabolites, pathways dysregulated disease. Exploring multiomics perspective concurrent data integration may provide new suitable therapeutic solutions combat pandemic.

Language: Английский

Citations

68
Pathogenesis of Respiratory Viral and Fungal Coinfections DOI
Fabián Salazar, Elaine Bignell, Gordon D. Brown

et al.

Clinical Microbiology Reviews, Journal Year: 2021, Volume and Issue: 35(1)

Published: Nov. 17, 2021

Individuals suffering from severe viral respiratory tract infections have recently emerged as "at risk" groups for developing invasive fungal infections. Influenza virus is one of the most common causes acute lower worldwide. Fungal complicating influenza pneumonia are associated with increased disease severity and mortality, pulmonary aspergillosis being manifestation. Strikingly, similar observations been made during current coronavirus 2019 (COVID-19) pandemic. The copathogenesis coinfections complex involves a dynamic interplay between host immune defenses virulence microbes involved that often results in failure to return homeostasis. In this review, we discuss main mechanisms underlying susceptibility following A comprehensive understanding these interactions will aid development therapeutic modalities against newly identified targets prevent treat emerging coinfections.

Language: Английский

Citations

61
Hematopoietic responses to SARS-CoV-2 infection DOI Creative Commons
Shokrollah Elahi

Cellular and Molecular Life Sciences, Journal Year: 2022, Volume and Issue: 79(3)

Published: March 1, 2022

Under physiological conditions, hematopoietic stem and progenitor cells (HSPCs) in the bone marrow niches are responsible for highly regulated interconnected hematopoiesis process. At same time, they must recognize potential threats respond promptly to protect host. A wide spectrum of microbial agents/products consequences infection-induced mediators (e.g. cytokines, chemokines, growth factors) can have prominent impact on HSPCs. While COVID-19 starts as a respiratory tract infection, it is considered systemic disease which profoundly alters system. Lymphopenia, neutrophilia, thrombocytopenia, stress erythropoiesis hallmark SARS-CoV-2 infection. Moreover, thrombocytopenia blood hypercoagulability common among patients with severe disease. Notably, invasion erythroid precursors progenitors by cardinal feature may part explain mechanism underlying hypoxia. These pieces evidence support notion skewed steady-state following The functional these alterations depend magnitude effect, launches unique response that associated increased myeloid at expense decreased lymphoid cells. This article reviews some key pathways including infectious inflammatory processes control hematopoiesis, followed comprehensive review summarizes latest discusses how infection impacts hematopoiesis.

Language: Английский

Citations

53
SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells DOI Creative Commons
Quirin Hammer, Josefine Dunst, Wanda Christ

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 38(10), P. 110503 - 110503

Published: Feb. 21, 2022

Natural killer (NK) cells are innate immune that contribute to host defense against virus infections. NK respond severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and activated patients with disease 2019 (COVID-19). However, by which mechanisms detect SARS-CoV-2-infected remains largely unknown. Here, we show the Non-structural protein 13 of SARS-CoV-2 encodes for a peptide is presented human leukocyte antigen E (HLA-E). In contrast self-peptides, viral prevents binding HLA-E inhibitory receptor NKG2A, thereby rendering target susceptible cell attack. line these observations, NKG2A-expressing particularly COVID-19 proficiently limit replication infected lung epithelial vitro. Thus, data suggest abrogates inhibition NKG2A+ cells, resulting missing self-recognition.

Language: Английский

Citations

52
Longitudinal characterization of circulating neutrophils uncovers phenotypes associated with severity in hospitalized COVID-19 patients DOI Creative Commons
Thomas J. LaSalle, Anna L.K. Gonye, Samuel S. Freeman

et al.

Cell Reports Medicine, Journal Year: 2022, Volume and Issue: 3(10), P. 100779 - 100779

Published: Sept. 26, 2022

Mechanisms of neutrophil involvement in severe coronavirus disease 2019 (COVID-19) remain incompletely understood. Here, we collect longitudinal blood samples from 306 hospitalized COVID-19+ patients and 86 controls perform bulk RNA sequencing enriched neutrophils, plasma proteomics, high-throughput antibody profiling to investigate relationships between states severity. We identify dynamic switches six distinct subtypes. At days 3 7 post-hospitalization, with display a granulocytic myeloid-derived suppressor cell-like gene expression signature, while resolving show progenitor-like signature. Humoral responses are identified as potential drivers effector functions, elevated acute respiratory syndrome 2 (SARS-CoV-2)-specific immunoglobulin G1 (IgG1)-to-IgA1 ratios who survived. In vitro experiments confirm that patient-derived IgG antibodies induce phagocytosis healthy donor IgA predominantly cell death. Overall, our study demonstrates dysregulated myelopoietic response COVID-19 role for IgA-dominant contributing mortality.

Language: Английский

Citations

52
Temporal changes in T cell subsets and expansion of cytotoxic CD4+ T cells in the lungs in severe COVID-19 DOI
Naoki Kaneko, Julie Boucau, Hsiao-Hsuan Kuo

et al.

Clinical Immunology, Journal Year: 2022, Volume and Issue: 237, P. 108991 - 108991

Published: March 29, 2022

Language: Английский

Citations

47
Defining the role of natural killer cells in COVID-19 DOI
Madeline Lee, Catherine A. Blish

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(10), P. 1628 - 1638

Published: July 17, 2023

Language: Английский

Citations

36
COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types DOI Creative Commons
Benjamin Joachim Schmiedel,

Job Rocha,

Cristian González-Colín

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Nov. 19, 2021

Abstract Common genetic polymorphisms associated with COVID-19 illness can be utilized for discovering molecular pathways and cell types driving disease pathogenesis. Given the importance of immune cells in pathogenesis illness, here we assessed effects COVID-19-risk variants on gene expression a wide range types. Transcriptome-wide association study colocalization analysis revealed putative causal genes specific where is most influenced by variants. Notable examples include OAS1 non-classical monocytes, DTX1 B cells, IL10RB NK CXCR6 follicular helper T CCR9 regulatory ARL17A H 2 cells. By transposase accessible chromatin H3K27ac-based chromatin-interaction maps types, prioritized potentially functional Our highlights potential risk to impact function diverse influence severe manifestations.

Language: Английский

Citations

54